Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis free of hepatic fibrosis and infiltration of inflammatory cells, and nonalcoholic steatohepatitis (NASH) accompanied by hepatic fibrosis and infiltration of inflammatory cells.
As the onset mechanism of NASH, a two-hit theory is widely supported, wherein triglyceride deposition (fatty liver) occurs in hepatocytes (first hit), and a cause of hepatocellular injury (second hit) thereon triggers the onset. It is assumed that the first hit is caused by the uptake, synthesis and catabolism of fatty acid and triglyceride release by hepatocytes, and the second hit is caused by oxidation stress, endotoxin, adipocytokine and the like (non-patent reference 1).
At the time of diagnosis, cirrhosis occurs in association with 2-28% of NASH a complication and, even in the case of NASH not in association with cirrhosis as a complication, about 20% is considered to progress to cirrhosis in about 10 years. The diagnostic and therapeutic methods of chronic hepatitis B and chronic hepatitis C, which are important causes of cirrhosis and liver cancer, are being established in recent years. In contrast, as for NAFLD and NASH, which are the other important causes of cirrhosis and liver cancer, elucidation of their pathology has just begun, and establishment of diagnostic methods and therapeutic methods is urgently needed. In non-patent reference 2, the onset and progress mechanism of NASH is considered using a hepatocyte specific Pten knockout mouse.
NAFLD often accompanies complications such as obesity, diabetes, hyperlipidemia, hypertension and the like, and is considered a metabolic syndrome. In NASH, a drug therapy of obesity, diabetes, hyperlipidemia, hypertension and the like behind NASH is important (non-patent reference 3).
Of the diabetic drugs, however, an •-glucosidase inhibitor, a sulfonylurea agent, a fast-acting insulin secretagogue and the like have not been reported as prophylactic and/or therapeutic drugs for NASH. Of the therapeutic drugs for hyperlipidemia, moreover, nicotinic acid derivatives have not been reported as prophylactic and/or therapeutic drugs for NASH. Therefore, it is presumed that not all therapeutic drugs for obesity, diabetes, hyperlipidemia, hypertension and the like are effective for NASH.
Colestimide is known to act as a hypocholesterolemic agent, an antiobesitic agent, a postprandial hyperglycemia improving agent or an insulin sensitizer (patent references 1-4). However, it is not known whether colestimide is effective for the prophylaxis or treatment of NASH.    [patent reference 1] JP-A-60-209523    [patent reference 2]WO02/43761    [patent reference 3] WO03/011308    [patent reference 4] WO2005/092349    [non-patent reference 1] Medical Care Guide of NASH•NAFLD (ed. the Japan Society of Hepatology) BUNKODO CO., LTD (Bunkodo) p 14-23 published on Aug. 22, 2006    [non-patent reference 2] Liver, vol. 45, No. 11, 568-580 (2004)    [non-patent reference 3] Medical Care Guide of NASH•NAFLD (ed. the Japan Society of Hepatology), BUNKODO CO., LTD. p 40-42, published on Aug. 22, 2006